Antiviral potential of medicinal plants against HIV,HSV, influenza,hepatitis, and coxsackievirus: A systematic review

Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo studies met the inclusion criteria of this review. The inferences from scientific literature review, focusing on potential therapeutic consequences of medicinal plants on experimental models of HIV, HSV, influenza, hepatitis, and coxsackievirus have ascertained the curative antiviral potential of plants. Fifty‐four medicinal plants belonging to 36 different families having antiviral potential were documented. Out of 54 plants, 27 individually belong to particular plant families. On the basis of the work of several independent research groups, the therapeutic potential of medicinal plants against listed common viral diseases in the region has been proclaimed. In this context, the herbal formulations as alternative medicine may contribute to the eradication of complicated viral infection significantly. The current review consolidates the data of the various medicinal plants, those are Sambucus nigra, Caesalpinia pulcherrima, and Hypericum connatum, holding promising specific antiviral activities scientifically proven through studies on experimental animal models. Consequently, the original research addressing the development of novel nutraceuticals based on listed medicinal plants is highly recommended for the management of viral disorders.     

Aloe‐emodin: A review of its pharmacology,toxicity, and pharmacokinetics

Aloe‐emodin is a naturally anthraquinone derivative and an active ingredient of Chinese herbs, such as Cassia occidentalis, Rheum palmatum L., Aloe vera, and Polygonum multiflorum Thunb. Emerging evidence suggests that aloe‐emodin exhibits many pharmacological effects, including anticancer, antivirus, anti‐inflammatory, antibacterial, antiparasitic, neuroprotective, and hepatoprotective activities. These pharmacological properties lay the foundation for the treatment of various diseases, including influenza virus, inflammation, sepsis, Alzheimer's disease, glaucoma, malaria, liver fibrosis, psoriasis, Type 2 diabetes, growth disorders, and several types of cancers. However, an increasing number of published studies have reported adverse effects of aloe‐emodin. The primary toxicity among these reports is hepatotoxicity and nephrotoxicity, which are of wide concern worldwide. Pharmacokinetic studies have demonstrated that aloe‐emodin has a poor intestinal absorption, short elimination half‐life, and low bioavailability. This review aims to provide a comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of aloe‐emodin reported to date with an emphasis on its biological properties and mechanisms of action.     

A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products

Black elder (Sambucus nigra L.) has a long ethnobotanical history across many disparate cultures as a treatment for viral infection and is currently one of the most‐used medicinal plants worldwide. Until recently, however, substantial scientific research concerning its antiviral properties has been lacking. Here, we evaluate the state of current scientific research concerning the use of elderberry extract and related products as antivirals, particularly in the treatment of influenza, as well as their safety and health impacts as dietary supplements. While the extent of black elder's antiviral effects are not well known, antiviral and antimicrobial properties have been demonstrated in these extracts, and the safety of black elder is reflected by the United States Food and Drug Administration approval as generally recognized as safe. A deficit of studies comparing these S. nigra products and standard antiviral medications makes informed and detailed recommendations for use of S. nigra extracts in medical applications currently impractical. Copyright © 2017 John Wiley & Sons, Ltd.     

Anxiolytic‐Like Effect of Illicium verum Fruit Oil,trans‐Anethole and Related Compounds in Mice

The fruit of Illicium verum Hook. f. (star anise) is used by many as a spice. The fragrance of I. verum fruit is characteristically anise‐like. In this study, hexane‐extracted I. verum fruit oil (IVO), trans‐anethole as the main component, and related compounds (propiophenone, 4′‐methoxy‐propiophenone, trans‐β‐methylstyrene) were analyzed in order to clarify the emotional effect of inhaling the fragrance of I. verum fruit. As a result, although 4 μL/L air IVO did not exhibit an anxiolytic‐like effect, 1 μL/L air trans‐anethole exhibited a significant effect (p < 0.05). Moreover, the anxiolytic‐like effect of 1 μL/L air trans‐anethole was significantly greater than 1 μL/L air propiophenone and 1 μL/L air 4′‐methoxy‐propiophenone (p < 0.05). Thus, the anxiolytic‐like effect of trans‐anethole was confirmed, and it is proposed that the methoxyl group and 1‐propenyl group in the para position of the benzene ring are necessary for the effect. Copyright © 2014 John Wiley & Sons, Ltd.     

傅里叶变换拉曼光谱法鉴别八角茴香及其伪品

目的：鉴别八角茴香及其伪品。方法：傅里叶拉曼光谱法（FT－Raman)。结果：八角茴香及其伪品在拉曼光谱中均有各自的特征峰,极易将它们区别开。结论：该方法快速准确,操作简单,不需分离,可直接测定。     

Bioactivity‐guided Fractionation of Phyllanthus orbicularis and Identification of the Principal Anti HSV‐2 Compounds

The antiherpes virus properties of Phyllanthus orbicularis Kunth, a Cuban‐endemic medicinal plant, have been reported previously but data on its phytochemical profile and identification of antiviral metabolites as well as their mechanisms of action are still lacking. In this work, a bioactivity‐guided phytochemical analysis was performed in order to isolate anti HSV‐2 compounds. P. orbicularis contained mainly phenolic acids derivatives and flavonoids. The antiviral effects were attributed to (?)‐epicatechin‐3‐O‐gallate (EC₅₀ = 11.7 µg/mL), procyanidins B1 and B2 (EC₅₀ = 32.8 µg/mL and 24.2 µg/mL, respectively) as well as oligomeric and polymeric procyanidins and their gallate derivatives. The antiviral mechanisms of the active P. orbicularis extracts and fractions were also investigated and the inhibition of several HSV‐2 early replication events and DNA synthesis were observed. This is the first study of extensive fractionation and phytochemical characterization of phenolic compounds from this species. Copyright © 2012 John Wiley & Sons, Ltd.     

八角茴香挥发油水提取工艺优化研究

目的：研究水蒸气提取分离八角茴香挥发油的最佳工艺条件。方法：以水为溶剂,采用蒸馏法考察不同料剂比下八角茴香挥发油的出油率,于隔夜静置后水浴加热对油水混合物进行分离。结果：料剂比为1：lO（g／mL）,粒径为60目,蒸出油水混合物为30mL时,出油率最高,约为4．9％;将收集的油水混合物静置过夜,于40℃下在水浴锅中加热20min,即可分离除去水得到小茴香挥发油。结论：该法简单易操作,无有机溶剂残留,耗时短,收率稳定,可为八角茴香挥发油的工业化提取及生产提供理论依据。     

不同制备工艺对肺毒清体外抗病毒作用的影响

目的:考察不同制备工艺对肺毒清处方药物体外抗病毒作用的影响.方法:采用体外抗病毒法对比肺毒清的水提取物(A)、水醇提取物(D)、水提醇沉物(B)及水提醇沉物的正丁醇萃取物(C)的抗病毒作用.结果:样品D在1 250 nmg·L-1下能完全抑制甲1型和甲3型流感病毒,250 mg·L-1样品A在60％细胞毒性下能完全抑制甲1型及甲3型流感病毒,其他样品对其他呼吸道病毒均无抑制作用,且样品D的体外抗病毒作用较样品A更好.结论:相同处方不同制备工艺对复方的药效作用具有一定影响.     

八角茴香油精馏釜底残液中1个新的苯甲醛类化合物

目的研究八角茴香油精馏釜底残液的化学成分。方法运用多种色谱方法进行分离纯化,根据理化性质和波谱数据鉴定化合物的结构。结果从八角茴香油精馏釜底残液中得到2个化合物,分别鉴定为(E)-1,4-二(4-甲氧基苯基)-3-丁烯-2-酮(1)和4-羟基-3-(3-甲基-3-丁烯-2-基)苯甲醛(2)。结论化合物1的核磁数据为首次报道,化合物2为新化合物。     

Antiviral activity of puerarin as potent inhibitor of influenza virus neuraminidase

Puerarin is a major isofiavone compound isolated from the root of Pueraria lobata. It was reported that puerarin had antioxidant, antiinflammatory, antitumor, cholesterol lowering, liver protective, and neuroprotective properties. However, few studies have explored the antiviral effect of puerarin and its target mechanism related to influenza virus. Here, the antiinfluenza activity of puerarin in vitro and in vivo and its mode of action on the potential inhibition of neuraminidase (NA) were investigated. Puerarin displayed an inhibitory effect on A/FM/1/1947(H1N1) (EC₅₀ = 52.06 μM). An indirect immunofluorescence assay indicated that puerarin blocked the nuclear export of viral NP. The inhibition of NA activity confirmed that puerarin can block the release of newly formed virus particles from infected cells. Puerarin (100 and 200 mg/kg/d) exhibited effective antiviral activity in mice, conferring 50% and 70% protection from death against H1N1, reducing virus titers, and effectively alleviating inflammation in the lungs. The molecular docking results showed that puerarin had a strong binding affinity with NA from H1N1. The results of the molecular dynamics simulation revealed that puerarin had higher stable binding at the 150‐loop region of the NA protein. These results demonstrated that puerarin acts as a NA blocker to inhibit influenza A virus both in cellular and animal models. Thus, puerarin has potential utility for the treatment of the influenza virus infection.     

Illicium verum: a review on its botany, traditional use, chemistry and pharmacology

Ethnopharmacological relevance

The fruit of Illicium verum Hook. f. (Chinese star anise) has long been used in traditional Chinese medicine and food industry with the actions of dispelling cold, regulating the flow of Qi and relieving pain.

Materials and methods

A bibliographic investigation was carried out by analyzing recognized books including Chinese herbal classic, and worldwide accepted scientific databases (Pubmed, SciFinder, Scopus and Web of Science) were searched for the available information on I. verum.

Results

I. verum is an aromatic evergreen tree of the family Illiciaceae. It is sometimes contaminated with highly toxic Japanese star anise (I. anisatum L.) and poisonous star anise (I. lanceolatum A. C. Smith), which contain several neurotoxic sesquiterpenes. Traditional uses of I. verum are recorded throughout Asia and Northern America, where it has been used for more than 10 types of disorders. Numerous compounds including volatiles, seco-prezizaane-type sesquiterpenes, phenylpropanoids, lignans, flavonoids and other constituents have been identified from I. verum. Modern pharmacology studies demonstrated that its crude extracts and active compounds possess wide pharmacological actions, especially in antimicrobial, antioxidant, insecticidal, analgesic, sedative and convulsive activities. In addition, it is the major source of shikimic acid, a primary ingredient in the antiflu drug (Tamiflu).

Aim of the review

This review summarizes the up-to-date and comprehensive information concerning the botany, traditional use, phytochemistry and pharmacology of I. verum together with the toxicology, and discusses the possible trend and scope for future research of I. verum.     

Aloe vera as an herbal medicine in the treatment of metabolic syndrome: A review

Metabolic syndrome (MS) is a highly prevalent health problem worldwide and is associated with different risk factors, including hyperglycemia, dyslipidemia, hypertension, and obesity. This condition increases the risk of developing type II diabetes mellitus and cardiovascular problems. The MS is one of the most important health concerns in industrialized countries and mainly results from a sedentary lifestyle, high levels of subjective stress, and unhealthy diets. Nowadays, the identification of appropriate health care approaches, such as herbal medicines, with fewer side effects is more favorable, especially with regard to the adverse effects of chemical drugs. Aloe barbadensis Miller known as Aloe vera is a useful plant with two major parts, including leaves that contain high concentrations of anthraquinone compounds and a clear gel. The gel is used as a food with several beneficial properties, such as antiinflammatory, antioxidant, antiviral, antibacterial, and wound‐healing features. Other effects of A. vera, such as its lipid‐lowering, antihypertensive, antidiabetic, antiobesity, and cardioprotective impacts, have been demonstrated in several studies. The present study was conducted to review the evidence on the pharmacological effects of A. vera on the different components of MS.     

Toxicity studies on dermal application of plant extract of Dodonaea viscosa used in Ethiopian traditional medicine

Despite advances in the understanding of the medicinal properties of many herbs, the consumer today is confronted with the lack of or misinformation concerning the safety of these herbs that rivals the heyday of the patent medicine era. In the present study, Dodonaea viscosa (Sapindaceae), a medicinal plant commonly used for skin diseases in Ethiopia was subjected to a systematic dermatotoxicity study. To this effect, the dermatotoxicity of an 80% methanol extract of the leaf was investigated in animals following standard procedures for irritation, sensitization, acute toxicity and repeated toxicity tests. The skin irritation test in rabbits showed the extract to be a slight or negligibly slight irritant, with a primary irritation index of 0.45. A sensitization test in mice by the mouse ear swelling test method revealed the extract to be a non‐sensitizer in the dose range 12–30 mg/mL. The percent responder was zero. The acute and repeated dermal toxicity tests on rats did not show any overt sign of toxicity. The findings of this study collectively indicate that dermal application of D. viscosa is not associated with any toxicologically relevant effects and the data could provide satisfactory preclinical evidence of safety to launch a clinical trial on a standardized formulation of the plant extracts. Copyright © 2009 John Wiley & Sons, Ltd.     

基于数据驱动分析的抗病毒中药分布规律

目的挖掘抗病毒中药分布规律,为中药抗病毒活性筛选和当前疫情防控候选方药筛选提供依据。方法以《抗病毒中草药的研究与应用》以及中国知网(CNKI)、Web of Science中的抗病毒中药文献为信息来源,对相关信息进行标准化处理,通过频数分析、共现分析及系统发育树构建方法挖掘具有抗病毒作用的中药药性、科属、有效成分及活性分布规律。结果共筛选出511味抗病毒中药,包含了新型冠状病毒肺炎(coronavirus disease 2019,COVID-19) "三药三方"所涉及的48味中药中的41味。它们多具有性寒、味苦,归肺经、肝经等药性,其中板蓝根、黄芩、金银花等最常见;涉及冠状病毒科数据135条,高频中药为柴胡、甘草、板蓝根等,且发现2003年非典时期研究最多的中药为板蓝根、苦豆子,而2020年COVID-19疫情时期,对桑白皮的研究占据首位;抗病毒中药的有效成分以多糖类、黄酮类为主;具有抗病毒作用的中药共涉及564个基原物种,在系统发育树上具有明显的聚集性,主要分布在种子植物门的菊分支和蔷薇分支,其中菊科、唇形科、豆科、蔷薇科等的抗病毒中药最多。结论抗病毒中药以味苦、性寒,归肺经、肝经为主,来源菊科、唇形科、豆科等科属中药更有可能具有抗病毒作用,其有效组分多为黄芪多糖、板蓝根多糖、槲皮素、咖啡酸、熊果酸等多糖类或黄酮类成分,而且这些规律与抗COVID-19疫情中推广使用的"三药三方"基本一致,这为抗病毒中药活性筛选,尤其为当前COVID-19疫情防控候选中药的筛选提供了参考依据。     

Formula Optimization of the Jiashitang Scar Removal Ointment and Antiinflammatory Compounds Screening by NF‐κB Bioactivity‐guided Dual‐luciferase Reporter Assay System

Inflammation plays a role in scar formation; therefore, decreasing inflammation benefits scar removal. Jiashitang scar removal ointment (JST) is a commercially available traditional Chinese medicinal formulation. It is composed of extracts from Carthamus tinctorius L. (Car), Rheum officinale Baill. (Rhe), Salvia miltiorrhiza Beg. (Sal), and Panax notoginseng (Burk.) F. H. Chen (Pan), which are all herbs with potent antiinflammatory activities. Our aims are to optimize the formula of JST and to elucidate its antiinflammatory active components. Response surface methodology was applied to optimize proportions of the four herb extracts. The antiinflammatory effects were evaluated using in vitro and in vivo models. To screen for active components in this formula, a bioactivity‐based ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry analysis was performed. After optimization, the antiinflammatory effects of the new formula were significantly superior to the original one. Screening identified 13 active ingredients: a series of saffiomin, emodin, salvianolic acid, tanshinone, and triterpenoid saponin derivatives. These active ingredients were predicted to exert nuclear factor‐κB inhibiting effects through MAPK, PI3K/AKT, and NIK‐IKK pathways. In conclusion, the original formula was successfully optimized with more potent antiinflammatory activity. These methods can be applied to researches of other formulas. Copyright © 2014 John Wiley & Sons, Ltd.     

Quercetin 3-rhamnoside exerts antiinfluenza A virus activity in mice

Our previous report showed that quercetin 3‐rhamnoside (Q3R) possessed antiviral activity against influenza A/WS/33 virus in vitro. The present study evaluated the effect of Q3R on influenza A/WS/33 virus infected mice. Mice orally treated with Q3R (6.25 mg/kg per dose) at 2 h before and once daily for 6 days after influenza virus infection showed significant decreases in weight loss, and decreased mortality. Lung virus titers of mice killed at 6 days after infection were about 2000 times lower than that of the placebo‐treated control mice and about two times lower than that for the oseltamivir‐treated mice. Furthermore, histological evaluation showed that administration of Q3R delayed the development and progression of pulmonary lesions. Therefore, Q3R could be an attractive lead for the development of antiviral agents against influenza virus. Copyright © 2011 John Wiley & Sons, Ltd.     

滇南八角果挥发油的气相色谱-质谱分析

用GC-MS从滇南八角果挥发油中共检出68个成分,鉴定了其中60个化合物,其中未发现含八角茴香油的主成分茴香醚和致癌成分黄樟醚。     

Phytochemical Characterization,Antibacterial, Acetylcholinesterase Inhibitory and Cytotoxic Properties of Cryptostephanus vansonii,an Endemic Amaryllid

Cryptostephanus vansonii I. Verd., an endemic Amaryllidaceae species from Zimbabwe, was evaluated for its acetylcholinesterase (AChE) inhibitory and cytotoxicity properties using Ellman's colorimetric method and the tetrazolium‐based colorimetric assay against Vero monkey kidney cells, respectively. The plant extracts were also evaluated for their antibacterial activity against five bacteria. Furthermore, phytochemical profiles of the extracts were determined using ultra‐high performance liquid chromatography coupled with tandem mass spectrometry analysis. A plant part‐dependent AChE inhibitory activity was observed, in the order, root > rhizome > basal leaf > leaf. Overall, C. vansonii extracts exhibited better antibacterial activity against Gram‐negative compared with Gram‐positive bacteria. Cytotoxic effects were not detected in Vero monkey kidney cell lines suggesting the possible absence of toxophores in C. vansonii extracts. Similar to the trend in biological activity, a distinct plant part‐dependent variation in hydroxybenzoates, hydroxycinnamates and flavonoids was observed in the plant extracts. In addition, 5‐hydroxymetylfurfural and eucomic acid were detected in the different plant parts of C. vansonii. The results of the present study provide valuable AChE inhibition activity, toxicological and phytochemical profiles of C. vansonii. Further studies on isolation of bioactive compounds and their subsequent evaluation in other pharmacological and toxicological model systems are required. Copyright © 2017 John Wiley & Sons, Ltd.     

Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells

Glycyrrhiza glabra L. (Fabaceae), commonly known as ‘liquorice’, is a well‐known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet‐tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra. Copyright © 2015 John Wiley & Sons, Ltd.